Domestic cats are valuable research models for the study of genetic disease in humans, providing critical insight into pathology and treatment options, including emerging gene therapies. However, maintenance of cat models can be expensive and challenging due to disease manifestations that interfere with normal reproduction. Genome resource banking, in conjunction with ART, offers a powerful alternative method for research model management and preservation. In addition, this technology may benefit conservation of the world's 36 biologically-imperiled wild cat species. The usefulness of this approach ultimately depends upon applying effective methods for embryo production, cryopreservation, and embryo transfer (ET). In the proposed resource-related research grant, our primary goal is to establish a functional genome resource bank for propagating, managing, and preserving cat disease models and other rare felids. Specific aims include investigating the potential of somatic cell cloning in cats while improving current embryo culture, cryopreservation and transfer methods for more efficient production of offspring, and then applying these techniques to propagation and preservation of fourteen feline models of human hereditary disease and two endangered nondomestic felid species. Initial studies will investigate somatic cell nuclear transfer, embryo culture requirements, alternative cryopreservation and recipient synchronization protocols, and embryo biopsy and diagnostic testing methods. Applied studies will examine the use of embryo cryopreservation and transfer for propagating mucopolysaccharidosis-affected kittens within clinical therapy trials and the feasibility of using somatic cell cloning, embryo cryopreservation and transfer for propagation of other disease models and nondomestic felids. Potential benefits include more productive use of research models, improving animal welfare, expanding usefulness of underutilized models, improving logistics and providing long-term preservation of valuable felid populations.